Genistein modulates the anti-tumor activity of cisplatin in MCF-7 breast and HT-29 colon cancer cells

The function of genistein (GEN) on tumor prevention and tumor promotion is discussed controversially. A possible interference of GEN with chemotherapy has been only rarely addressed so far. In this study, effects of GEN on the anti-tumor activity of cisplatin (CIS) were investigated in the presence and absence of estradiol (10^?10 M) in MCF-7 breast and HT-29 colon cancer cells. Cells were treated with graded concentrations of GEN (10^?4–10^?6 M), E₂, CIS and combinations. Cell growth, proliferation and apoptosis were determined as well as the expression level of PCNA, Ki67 and BCL-2 family members. CIS and GEN 10^?4 M inhibited cell growth and induced apoptosis in MCF-7 and HT-29 cells in the presence and absence of E₂. Co-treatment with CIS and 10^?4M GEN resulted in additive effects. In concentrations of 10^?5 and 10^?6 M, GEN stimulated cell growth in MCF-7 cells. It promoted proliferation, inhibited apoptosis and counteracted the anti-tumor activity of CIS in MCF-7 and HT-29 cells. Particularly the ability of CIS to induce apoptosis was antagonized. In ER alpha-positive MCF-7 cells, but not in ER alpha-negative HT-29 cells, E₂ was able to neutralize the anti-CIS effects of GEN. Our data provide evidence that GEN in the absence of E₂, a situation which occurs in postmenopausal women, directly affects the anti-tumor activity of cytostatic drugs like CIS. The exact molecular mechanism has to be investigated in future studies.     

Tl(I) and Tl(III) alter the expression of EGF‐dependent signals and cyclins required for pheochromocytoma (PC12) cell‐cycle resumption and progression

The effects of thallium [Tl(I) and Tl(III)] on the PC12 cell cycle were evaluated without (EGF^?) or with (EGF⁺) media supplementation with epidermal growth factor (EGF). The following markers of cell‐cycle phases were analyzed: cyclin D1 (G₁); E2F‐1, cyclin E and cytosolic p21 (G₁→S transition); nuclear PCNA and cyclin A (S); and cyclin B1 (G₂). The amount of cells in each phase and the activation of the signaling cascade triggered by EGF were also analyzed. Tl(I) and Tl(III) (5–100 μM) caused dissimilar effects on PC12 cell proliferation. In EGF^? cells, Tl(I) increased the expression of G₁→S transition markers and nuclear PCNA, without affecting cyclin A or cyclin B1. In addition to those, cyclin B1 was also increased in EGF⁺ cells. In EGF^? cells, Tl(III) increased the expression of cyclin D1, all the G1→S and S phase markers and cyclin B1. In EGF⁺ cells, Tl(III) increased cyclin D1 expression and decreased all the markers of G₁→S transition and the S phase. Even when these cations did not induce the activation of EGF receptor (EGFR) in EGF^? cells, they promoted the phosphorylation of ERK1/2 and Akt. In the presence of EGF, the cations anticipated EGFR phosphorylation without affecting the kinetics of EGF‐dependent ERK1/2 and Akt phosphorylation. Altogether, results indicate that Tl(I) promoted cell proliferation in both EGF^? and EGF⁺ cells. In contrast, Tl(III) promoted the proliferation of EGF^? cells but delayed it in EGF⁺ cells, which may be related to the toxic effects of this cation in PC12 cells. Copyright © 2014 John Wiley & Sons, Ltd.     

Immunosuppressive constituents from Urtica dentata Hand

A novel biscoumarin, 6,6′,7,7′-tetramethoxyl-8,8′-biscoumarin (1), was isolated from the ethyl acetate extract of Urtica dentata Hand, together with five known compounds named as 7,7′-dihydroxy-6,6′-dimethoxy-8,8′-biscoumarin (2), 7,7′-dimethoxy-6,6′-biscoumarin (3), scoparone (4), vanillic acid (5), and daucosterol (6). Structures of the isolated compounds were elucidated on the basis of spectroscopic analysis including 2D NMR experiments. Compounds 1 and 2 were confirmed to be a rare carbon–carbon linked symmetrical biscoumarin. Compounds 1–4, especially 1 (IC₅₀ = 8.18 × 10^? 5 mol/l), showed potent immunosuppressive activities as determined by the Cell Counting Kit-8 assay for lymphocyte proliferation. Also, in the FACS analysis, 1 (IC₅₀ = 5.19 × 10^? 4 mol/l) promoted the differentiation of CD4⁺CD25⁺Foxp3⁺ T regulatory cells distinctly compared to the normal control. Thus, 1 possessed specific immunosuppressive property by eliciting T regulatory cells, which may provide a potential treatment strategy for autoimmune diseases.     

Curcumin enhanced antiproliferative effect of mitomycin C in human breast cancer MCF-7 cells in vitro and in vivo

Aim:

To investigate the efficacy of mitomycin C (MMC) in combination with curcumin in suppressing human breast cancer in vitro and in vivo.

Methods:

Human breast cancer MCF-7 cells were used. Cell viability was measured using MTT assay. The cell cycle phase was detected with flow cytometric analysis. Cell cycle-associated proteins were examined using Western blot analysis. MCF-7 breast cancer xenografts were established to monitor tumor growth and cell cycle-associated protein expression.

Results:

Curcumin inhibited MCF-7 breast cancer cell viability in a concentration-dependent manner (IC₅₀ value=40 μmol/L). Similarly, MMC inhibited the cell viability with an IC₅₀ value of 5 μmol/L. Combined treatment of MMC and curcumin showed a synergistic antiproliferative effect. In the presence of curcumin (40 μmol/L), the IC₅₀ value of MMC was reduced to 5 μmol/L. In MCF-7 xenografts, combined administration of curcumin (100 mg/kg) and MMC (1-2 mg/kg) for 4 weeks produced significantly greater inhibition on tumor growth than either treatment alone. The combined treatment resulted in significantly greater G₁ arrest than MMC or curcumin alone. Moreover, the cell cycle arrest was associated with inhibition of cyclin D1, cyclin E, cyclin A, cyclin-dependent kinase 2 (CDK2) and CDK4, along with the induction of the cell cycle inhibitor p21 and p27 both in MCF-7 cells and in MCF-7 xenografts. These proteins were regulated through p38 MAPK pathway.

Conclusion:

The results suggest that the combination of MMC and curcumin inhibits MCF-7 cell proliferation and cell cycle progression in vitro and in vivo via the p38 MAPK pathway.     

Synthesis of a novel phosphate analog of 20-hydroxylecdysone with potent hypoglycemic activity

A novel, water-soluble 20-hydroxylecdysono-20,22-phosphoric acid 2 and its sodium salt 3 were designed and synthesized from 20-hydroxylecdysone 1 in six steps and with 67% overall yield. The synthesized phosphoric acid 2 exhibited hypoglycemic activity >40-fold more potent than that of 20-hydroxylecdysone 1 at concentrations between 2 × 10^? 7 and 2 × 10^? 8 mol/l in a glucose consumption test in HepG2 cells. At a concentration of 2 × 10^? 9 mol/l, phosphoric acid 2 was still active, causing a maximum increase in glucose consumption of more than 500%, while 20-hydroxylecdysone 1 was inactive.     

Regulation of CD1, Ki-67, PCNA mRNA expression,and Akt activation in estrogen-responsive human breast adenocarcinoma cell line,MCF-7 cells,by griffonianone C,an isoflavone derived from Millettia griffoniana

Context: Millettia griffoniana Baill. (Fabaceae), which contains isoflavonoids like griffonianone C (Griff C), is commonly used in the folk medicine in Cameroon to treat various ailments. Possible health benefits of Griff C which include alleviation of menopausal symptoms, limitation of bone resorption, and lowering of the risks of cancer and cardiovascular diseases attracted our interest.

Objective: The effects of Griff C on the regulation of the expression of proliferation markers such as proliferating cell nuclear antigen (PCNA), cyclin D1 (CD1) and Ki-67 are investigated here. Its role in apoptosis or cell survival, through the phosphatidylinositol 3 kinase-Akt (PI3K-Akt) signaling pathway is further studied.

Materials and methods: Semiquantitative real-time PCR was performed to analyze the effects of Griff C on gene expression in MCF-7 cells. Western blot analysis was used to assess the role of Griff C on the expression of phosphorylated Akt in MCF-7 cells.

Results: Griff C induced a 4.84-fold increase in the expression of Ki-67 mRNA at the concentration of 10^?8 M and a 3.90-fold increase of CD1 mRNA at 10^?7 M. Griff C slightly increased the phosphorylation of Akt at its serine 473 residue. Akt phosphorylation was inhibited by the PI3K inhibitor, LY294002, but not by the specific estrogen receptor antagonist, fulvestrant.

Discussion and conclusion: These findings suggest that Griff C can modulate proliferation of MCF-7 cells. Our results also suggest that Griff C can affect the PI3K-related signaling pathway. Thus, Griff C may exert part of its low proliferative and antiapoptotic effects by a nongenomic mode of action.     

Emodin induces cytotoxic effect in human breast carcinoma MCF-7 cell through modulating the expression of apoptosis-related genes

Abstract

Context: The poor prognostic outcome of breast cancer is largely due to its resistance to cancer therapies. Development of therapeutic agents that can inhibit growth and induce apoptosis in breast cancer cells can help solve the problem. Emodin is an active anthraquinone that has been reported to have diverse biological effects.

Objective: In this study, the anticancer effects of emodin on growth inhibition, apoptosis induction and the expression of apoptosis-related genes in MCF-7 cells were investigated.

Materials and methods: Growth inhibition induced by emodin was investigated by the MTS assay and the colony formation assay; while emodin-induced apoptosis was determined by the COMET assay and DNA fragmentation detection. Emodin (35?μM)-induced alterations in the expression of apoptotic-related genes were detected by using real-time PCR.

Results: Emodin had significant growth inhibitory effects on MCF-7 cells with IC₅₀?=?7.22?µg/ml (～30?μM). It also exerted a concentration-dependant inhibitory effect on the colony-forming ability of MCF-7 cells with IC₅₀?=?7.60?µg/ml (～30?µM). Hallmarks of apoptosis, such as single-strand DNA breakage and DNA fragmentation, were observed in emodin-treated MCF-7 cells. The gene expression of Fas ligand (FASL) was up-regulated (p?<?0.01) but those of MCL1, CCND1 and C-MYC were down-regulated (p?<?0.05) in emodin-treated MCF-7 cells.

Discussion and conclusion: This study indicated that emodin could induce growth inhibition and apoptosis in MCF-7 cells through the modulation of the expression of apoptosis-related genes. The growth inhibitory effects of emodin might involve both the intrinsic and the extrinsic apoptotic pathways and cell cycle arrest.     

人参皂苷Rg3对乳腺癌MCF-7细胞增殖和侵袭的影响

目的 观察人参皂苷Rg3对雌激素受体阳性的乳腺癌细胞MCF-7增殖和侵袭的影响,并探讨其可能的作用机制。方法 采用MTT法检测细胞的增殖能力,流式细胞仪分析细胞周期分布以及凋亡比率,通过Transwell小室观察细胞侵袭力,RT-PCR法检测细胞中的MMP-9 mRNA的表达。结果 与对照组相比,人参皂苷Rg3能显著抑制MCF-7细胞的增殖;G₀/G₁期及S期细胞比例减少,而G₂/M期细胞比例显著增加;同时细胞凋亡比率亦明显提升,而细胞侵袭指数降低,且呈现良好的剂量、时间依赖性。同时人参皂苷Rg3还能显著抑制细胞中MMP-9 mRNA的表达水平(P<0.05)。结论 人参皂苷Rg3能抑制MCF-7细胞的增殖和侵袭,其作用机制可能与其能降低MMP-9基因的表达有关。     

A new N-methoxyl-carbonyl benzylisoquinoline from Litsea cubeba

A new benzylisoquinoline alkaloid (?)-N-methoxycarbonyl-norjuziphine (1) was isolated from Litsea cubeba. Its structure was identified by extensively spectroscopic techniques and confirmed by the single-crystal X-ray diffraction analysis. Compound 1 showed cytotoxicity against HL-60 and MCF-7 cells, with IC₅₀ values of 18.1 and 15.0 μM, respectively, comparable to 3.1 and 17.5 μM of the cisplatin (positive control).     

Nardostachys chinensis induces granulocytic differentiation with the suppression of cell growth through p27Kip1 protein-related G0/G1 phase arrest in human promyelocytic leukemic cells

Abstract

Context: Nardostachys chinensis Batalin (Valerianaceae) has been used in Korean traditional medicine to elicit stomachic and sedative effects. However, the anti-leukemic activities of N. chinensis have not been well examined.

Objective: To investigate the effect of N. chinensis on differentiation and proliferation in the human promyelocytic leukemic HL-60 cells.

Materials and methods: The dried roots and stems of N. chiensis are extracted using hot water and then freeze-dried. The yield of extract was 12.82% (w/w). The HL-60 cells were treated with 25–200?μg/ml of N. chinensis for 72?h or 100?μg/ml of N. chinensis for 24–72?h.

Results: Nardostachys chinensis significantly inhibited cell viability dose dependently with an IC₅₀ of 100?μg/ml in HL-60 cells. Nardostachys chinensis induced differentiation of the cells as measured by reduction activity of NBT and expression of CD11b but not of CD14 as analyzed by flow cytometry, which indicates a differentiation toward the granulocytic lineage. Nardostachys chinensis also induced growth inhibition through G₀/G₁ phase arrest in the cell cycle of HL-60 cells. Among the G₀/G₁ phase in the cell cycle-related protein, the expression of cyclin-dependent kinase (CDK) inhibitor p27^Kip1 was increased in N. chinensis-treated HL-60 cells, whereas the expression levels of CDK2, CDK4, CDK6, cyclin D1, cyclin D3, cyclin E, and cyclin A were decreased. Interestingly, N. chinensis markedly enhanced the binding of p27^Kip1 with CDK2 and CDK6.

Discussion and conclusion: This study demonstrated that N. chinensis is capable of inducing cellular differentiation and growth inhibition through p27^Kip1 protein-related G₀/G₁ phase arrest in HL-60 cells.     

Novel anticancer alkene lactone from Persea americana

Abstract

Context: Persea americana Mill (Lauraceae) root bark is used in ethnomedicine for a variety of diseases including cancer.

Objective: To isolate and characterize the chemical constituent in P. americana, and also to determine the anticancer property of a new alkene lactone from the root bark of P. americana.

Materials and methods: The MCF-7 cells were treated with different concentrations of the pure compound for 48?h. The percentage of cells in the various phases, online monitoring of metabolic changes and integrin receptor expression determined by flow cytometry.

Results: One novel alkene lactone (4-hydroxy-5-methylene-3-undecyclidenedihydrofuran-2 (3H)-one) (1) was isolated and characterized using 1D-NMR, 2D-NMR, infrared, UV and MS. At a concentration of 10?µg/mL, significant reduction of proliferation of MCF-7 was induced while MCF-12?A cell was significantly stimulated by 10?µg/mL. The IC₅₀ value for MCF-7 cells is 20.48?µg/mL. Lower concentration of 1 harbor no significant effect on either MCF-7 or MCF-12A. The apoptotic rates of MCF-7 cells were increased significantly. At the final concentration 10?µg/mL, up to 80% of all breast cancer cells were dead. On the non-tumorigenic cell line MCF-12A, the same concentrations (1 and 10?µg/mL) of compound 1 caused significant enhanced apoptotic rates. A total of 1?µg/mL of 1 caused a decrease of α4-, α6-, β1- and β3-integrin expression.

Conclusions: The compound caused a stimulatory effect on non-tumorigenic MCF-12A cells with respect to cell adhesion while tumorigenic MCF-7 cells detached continuously. This is the first report on the anticancer effects of this class of compound.     

Antiproliferative activities of Garcinia bracteata extract and its active ingredient,isobractatin, against human tumor cell lines

In our cell based screening of antitumor ingredients from plants, the EtOH extract of Garcinia bracteata displayed antiproliferative effect against human lung adenocarcinoma A549 cells, human breast cancer MCF-7 cells, and human prostate cancer PC3 cells. Phytochemical investigation of this active extract produced nine ingredients, and their structures were established by analysis of MS and NMR spectra. Antiproliferative evaluation of isolated ingredients on A549, MCF-7 and PC3 cells indicated that a xanthone named isobractatin (1) exhibited potent antiproliferative activity against the above three human cancer cell lines with IC₅₀ values ranging from 2.90 to 4.15 μM. Treatment of PC3 cells with 1 led to an enhancement of the cell apoptosis, and arrested cell cycle in the G0/G1 phase. The G0/G1 phase cycle-related proteins analysis showed that the expressions of cyclins D1 and E were reduced by 1, whereas the protein level of cyclin dependent kinase (CDK) inhibitor P21 was induced. Additionally, 1 enhanced PC3 cell apoptosis by activations of Bax, caspases 3 and 9, and by inhibition of Bcl-2. Our combined data illustrated that isobractatin (1) was the antiproliferative ingredient of G. bracteata against three human cancer cell lines, which exerted its antiproliferatrive effect via cell cycle arrest and induction of apoptosis.     

Estrogenic activities of di-2-ethylhexyl phthalate

Phthalate esters are widespread in the environment. They have been described as being one of the most abundant man-made environmental contaminants that may be adverse to human health. Particularly, di-2-ethylhexyl phthalate (DEHP) has been shown to cause reproductive and developmental toxicity and is suspected to be an endocrine disruptor. The primary objective of this study is to determine the estrogenic activity of DEHP. Estrogenic activities of DEHP were studied by in vitro assays of human breast cancer MCF-7 cell proliferation. Estrogen-dependent MCF-7 cells were grown in RPMI1640 medium containing 10% fetal bovine serum. Five days before the addition of the test compounds, the cells were washed by phosphate balanced solution (PBS), and the medium was substituted with a phenol red-free RPMI1640 medium containing 5% dextral charcoalstripped Fetal Bovine Serum (FBS). Fresh medium was added to the respective test compounds and the control cell received only the vehicle (ethanol). The proliferation of MCF-7 cell was analyzed by the MTT assay, growth curves, mitotic index and colony forming efficiency. Compared with the ethanol control cells, the proliferation of tested cells treated with DEHP, like estradiol, was significantly enhanced and the activity of the cell proliferation reached the maximum at 1 × 10⁻³ mol/L DEHP. The relative proliferative potency of DEHP was 0.000 001 with a relative proliferative effect of 97.32%. During the log phase, the mitotic index of the tested cells treated with DEHP and estradiol was significantly increased. The cell cloning efficiency was enhanced, which was treated by 10⁻³ mol/L DEHP only for 48 hours. The results show a time-dependent and dose-dependent model. Di-2-ethylhexyl phthalate enhanced the proliferation of human breast cancer MCF-7 cells in vitro and might demonstrate an estrogenic activity.     

The effects of icariin on the expression of HIF-1α, HSP-60 and HSP-70 in PC12 cells suffered from oxygen–glucose deprivation-induced injury

Context: The effects of icariin, a chief constituent of ?avonoids from Epimedium brevicornum Maxim (Berberidaceae), on the levels of HIF-1α, HSP-60 and HSP-70 remain unknown.

Objective: To explore the effects of icariin on the levels of HSP-60, HIF-1α and HSP-70 neuron-specific enolase (NSE) and cell viability.

Materials and methods: PC12 cells were treated with icariin (10^?7, 10^?6 or 10^?5?mol/L) for 3?h (1?h before oxygen–glucose deprivation (OGD) plus 2?h OGD). HSP-60, HIF-1α, HSP-70 and NSE were measured using enzyme-linked immunosorbent assay (ELISA). Cell viability was determined by metabolic 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Results: After 2?h OGD, levels of HIF-1α, HSP-60, HSP-70 and NSE were increased significantly (HIF-1α: 33.3?±?1.9?ng/L, HSP-60: 199?±?16?ng/L, HSP-70: 195?±?17?ng/L, NSE: 1487?±?125?ng/L), and cell viability was significantly decreased (0.26?±?0.03), while icariin (10^?7, 10^?6, or 10^?5?mol/L) significantly reduced the contents of HIF-1α, HSP-60, HSP-70 and NSE (HIF-1α: 14.1?±?1.4, 22.6?±?1.8, 15.7?±?2.1, HSP-60: 100?±?12, 89?±?6, 113?±?11, HSP-70: 139?±?9, 118?±?7, 95?±?9 and NSE: 1121?±?80, 1019?±?52, 731?±?88), and improved cell viability (0.36?±?0.03, 0.38?±?0.04, 0.37?±?0.03) in OGD-treated PC12 cells.

Discussion and conclusion: These results indicate that the protective mechanisms of icariin against OGD-induced injury may be related to down-regulating the expression of HIF-1α, HSP-60 and HSP-70.     

Effects of ginsenoside compound K combined with cisplatin on the proliferation,apoptosis and epithelial mesenchymal transition in MCF-7 cells of human breast cancer

Context: Breast cancer seriously harms the health of women and there are currently few therapeutic options for patients with breast cancer.

Objective: Effects of ginsenoside compound K (CK) in combination with cisplatin (DDP) on the proliferation, apoptosis, and epithelial mesenchymal transition (EMT) of MCF-7 cells were studied.

Materials and methods: MCF-7 cells were divided into CK (50?μmol/L) group, DDP (10?mg/L) group, CK (50?μmol/L)?+DDP (10?mg/L) group, and control (CON) group. The cells in the CON group were not treated with any drugs. Proliferation, apoptosis, expression of E-cadherin, N-cadherin, vimentin, protein kinase B (Akt), phosphorylated Akt (p-Akt), and level of fibronectin (FN) in MCF-7 cells were detected by methyl thiazolyl tetrazolium (MTT), flow cytometry, western blotting, and enzyme-linked immuno sorbent assay (ELISA), respectively.

Results: The proliferation inhibition rates in CK, DDP, and CK?+?DDP groups at 48?h were 19.18?±?2.25, 21.34?±?2.84, and 43.37?±?5.62, respectively. The apoptosis rates were 2.85?±?0.56, 13.37?±?2.28, 20.04?±?2.92, and 30.78?±?4.64 at 24?h and 3.14?±?0.72, 20.36?±?3.28, 27.58?±?4.09, and 41.62?±?5.83 at 48?h in CON, CK, DDP, and CK?+?DDP groups, respectively. CK or DDP alone and their combination all could reduce the levels of N-cadherin, vimentin, p-Akt/Akt, and FN and elevate level of E-cadherin.

Discussion and conclusion: Both CK and DDP can inhibit the proliferation, EMT, and induce the apoptosis in MCF-7 cells, which may be related to the PI3K/Akt pathway. In addition, the combination of CK with DDP can produce a better effect.     

Homoisoflavanones with estrogenic activity from the rhizomes of Polygonatum sibiricum

A new homoisoflavanone, (3R)-5-hydroxy-7-methoxyl-3-(2′-hydroxy-4′- methoxybenzyl)-chroman-4-one (1), together with six known analogs, were isolated from the rhizomes of Polygonatum sibiricum. Their structures were elucidated on the basis of extensive spectroscopic analysis. All compounds were tested for their estrogenic activity using the MCF-7 estrogenresponsive human breast cancer cell lines. At a dose of 0.1 μmol/L, compounds 1–7 exhibited significant proliferative effects on MCF-7 cells compared with E₂. The molecular docking study results indicated that the activity of compounds 3, 5, 6, and 7 may be the binding with ERR.     

Design,synthesis and antibreast cancer MCF-7 cells biological evaluation of heterocyclic analogs of resveratrol

A new series of resveratrol heterocyclic analogs (4a–m) were designed and synthesized, and their inhibitiory effects on MCF-7 cells were evaluated to investigate structure–activity relationship. The effects of these analogs on human breast cancer MCF-7 cells were also determined. Results showed that MCF-7 cells could be inhibited more potently by these analogs than by resveratrol (IC₅₀ = 80.0 μM). Among the analogs, compounds 4c, 4e, and 4k showed a significantly higher activity (IC₅₀ = 42.7, 48.1, and 43.4 μM) than resveratrol. Furthermore, the derivatives without additional heterocyclic structure in the 4′-OH position exhibited a more potent activity than that with addition heterocyclic structure. In addition, docking simulation was performed to adequately position compound 4c in a human F₁-ATPase active site to determine a probable binding model. These heterocyclic analogs could be effective candidates for the chemoprevention of human breast cancer.     

莪术油对直肠癌SW1463细胞株增殖、凋亡及Caspase-3、Bax、Bcl-2蛋白表达的影响

目的 探讨莪术油对直肠癌SW1463细胞株增殖、凋亡及相关蛋白Caspase-3、Bax、Bcl-2表达的影响。方法 水蒸气蒸馏法提取黔产莪术挥发油,配制成40、80、120、160、200、240、280 mg/L浓度梯度,干预SW1463细胞24、48、72 h,MTT法检测莪术油对SW1463细胞的增殖抑制率;Giemsa染色法观察莪术油对SW1463细胞凋亡形态的影响;蛋白免疫印迹法（Western blotting）检测Capase-3、Bax与Bcl-2蛋白表达。结果 莪术油对SW1463细胞的增殖有明显抑制作用,并呈现时间-剂量相关性,24、48、72 h的半数抑制浓度（IC₅₀）分别为144.33、134.11、120.04 mg/L;Giemsa染色可见细胞明显的凋亡形态学特征;莪术油干预SW1463细胞24 h后,与对照组比较,Caspase-3、Bax蛋白表达显著上调、Bcl-2蛋白表达显著下调（P<0.05）。结论 莪术油能明显抑制SW1463细胞增殖,诱导细胞凋亡,其机制可能与上调Caspase-3和Bax蛋白表达、下调Bcl-2蛋白表达相关。     

Lignans from the stems of Sambucus williamsii and their effects on osteoblastic UMR106 cells

Three new lignans, sambucunol A (8) ((+)-erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(4-hydroxy-3-methoxycinnamoyloxypropanyl)-2-hydroxyphenoxy]-1, 3-propanediol), sambucunol B (9) ((+)-threo-1-(4-hydroxyl-3-methoxyphenyl)-2-[4-(4-hydroxy-3-methoxy-cinnamoyloxy propanyl)-2-hydroxyphenoxy]-1, 3-propanediol) and buddlenol G (10) (2-{4-[2, 3-dihydro-3-hydroxymethyl-7-hydroxy-5-(4-hydroxy-3-methoxycinnamoyloxypropanyl)-2-benzofuranyl]-2,6-dimethoxyphenoxy}-1-(4- hydroxy-3-methoxyphenyl) -1, 3-propanediol), along with seven known ones, including ( ? )-syringaresinol (1), ( ? )-pinoresinol (2), 1, 2-bis(4-hydroxy-3-methoxy phenyl)-1, 3-propanediol (3), ( ? )-erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxy propanyl)-2-methoxyphenoxy]-1, 3-propanediol (4), ( ? )-threo-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropanyl)-2-methoxy phenoxy]-1, 3-propanediol (5), ( ? )-lariciresinol (6) and ( ? )-dihydrodehydrodiconiferyl alcohol (7), were isolated from the 60% ethanol extract of stems of Sambucus williamsii Hance by chromatographic methods. Their structures were established by spectral analysis. The effects of isolated compounds on the osteoblast-like UMR106 cell proliferation and ALP activities were determined. Compounds 2, 7 and 10 showed stimulating effects both on UMR106 cell proliferation and ALP activity. Compounds 1, 3, 6 and 8 stimulated UMR106 cell proliferation, while compounds 4 and 5 induced ALP activity in UMR106 cell.